Xiang Kong1, Ming-Zhe Ma2, Li Qin3, Yan Zhang4, Xiao-Yong Li3, Guo-Dong Wang5, Qing Su6, Dao-You Zhang7. 1. Department of Endocrinology, Xinhua Hospital,Shanghai Jiaotong University School of Medicine, China Department of Pharmacology, Third-Grade Pharmacology Laboratory of State Administration of Traditional Chinese Medicine, Wannan Medical College,China. 2. Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China. 3. Department of Endocrinology, Xinhua Hospital,Shanghai Jiaotong University School of Medicine, China. 4. Department of Gastroenterology,Yijishan Hospital Affiliated to Wannan Medical College, China. 5. Department of Pharmacy, Wannan Medical College,China. 6. Department of Endocrinology, Xinhua Hospital,Shanghai Jiaotong University School of Medicine, China suqingxinhua@yahoo.com.cn yjszhangdaoyou@sina.com. 7. Department of Nephrology,Yijishan Hospital Affiliated to Wannan Medical College, China.
Abstract
INTRODUCTION: This study was designed to investigate the underlying mechanisms of synergistic antihypertensive effect produced by combination therapy of losartan and pioglitazone in metabolic syndrome (MS) rats. MATERIALS AND METHODS: An MS model was induced by feeding rats a high-fat, high-sodium diet and 20% sucrose solution. Losartan (20 mg/kg/day), pioglitazone (10 mg/kg/day), and their combination were orally administered for eight consecutive weeks. Systolic blood pressure (SBP) and mean arterial pressure (MAP) were measured using the tail-cuff method and carotid arterial catheterization, respectively. The aortas were isolated and in vitro vascular reactivity studies were performed. The protein expression of angiotensin type 1 receptor (AT1), endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox), level of nitrotyrosine as well as activity of eNOS and NADPH oxidase in aortas of MS rats were detected. RESULTS: After eight weeks of treatment, the SBP and MAP in the losartan (115 ± 5 and 106 ± 6 mmHg), pioglitazone (130 ± 6 and 118 ± 6 mmHg), and combination therapy (105 ± 6 and 98 ± 5 mmHg) groups were lower than those in the model group (150 ± 8 and 136 ± 9 mmHg). Combination therapy of losartan and pioglitazone reduced BP more than either monotherapy, and showed additive effects on improving endothelial dysfunction and abolishing the increased vascular responsiveness to angiotensin II. These synergistic effects were associated with further reductions in protein expression of p47(phox) and AT1, NADPH oxidase activity, and nitrotyrosine level. CONCLUSIONS: Our data indicate that combined treatment exerts more beneficial effects on lowering BP and improving vascular lesions.
INTRODUCTION: This study was designed to investigate the underlying mechanisms of synergistic antihypertensive effect produced by combination therapy of losartan and pioglitazone in metabolic syndrome (MS) rats. MATERIALS AND METHODS: An MS model was induced by feeding rats a high-fat, high-sodium diet and 20% sucrose solution. Losartan (20 mg/kg/day), pioglitazone (10 mg/kg/day), and their combination were orally administered for eight consecutive weeks. Systolic blood pressure (SBP) and mean arterial pressure (MAP) were measured using the tail-cuff method and carotid arterial catheterization, respectively. The aortas were isolated and in vitro vascular reactivity studies were performed. The protein expression of angiotensin type 1 receptor (AT1), endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox), level of nitrotyrosine as well as activity of eNOS and NADPH oxidase in aortas of MS rats were detected. RESULTS: After eight weeks of treatment, the SBP and MAP in the losartan (115 ± 5 and 106 ± 6 mmHg), pioglitazone (130 ± 6 and 118 ± 6 mmHg), and combination therapy (105 ± 6 and 98 ± 5 mmHg) groups were lower than those in the model group (150 ± 8 and 136 ± 9 mmHg). Combination therapy of losartan and pioglitazone reduced BP more than either monotherapy, and showed additive effects on improving endothelial dysfunction and abolishing the increased vascular responsiveness to angiotensin II. These synergistic effects were associated with further reductions in protein expression of p47(phox) and AT1, NADPH oxidase activity, and nitrotyrosine level. CONCLUSIONS: Our data indicate that combined treatment exerts more beneficial effects on lowering BP and improving vascular lesions.
Authors: Yang Yu; Bao-Jian Xue; Shun-Guang Wei; Zhi-Hua Zhang; Terry G Beltz; Fang Guo; Alan Kim Johnson; Robert B Felder Journal: Hypertension Date: 2015-06-22 Impact factor: 10.190
Authors: Roberto Palacios-Ramírez; Raquel Hernanz; Angela Martín; José V Pérez-Girón; María T Barrús; Zoe González-Carnicero; Andrea Aguado; Frederic Jaisser; Ana M Briones; Mercedes Salaices; María J Alonso Journal: Sci Rep Date: 2019-11-11 Impact factor: 4.379